dc.contributor.author | González-Corpas, Ana | |
dc.contributor.author | Cabezudo, Sofía | |
dc.contributor.author | López-Perrote, Andrés | |
dc.contributor.author | Degliesposti, Gianluca | |
dc.contributor.author | Zarzuela, Eduardo | |
dc.contributor.author | Skehel, J Mark | |
dc.contributor.author | Muñoz, Javier | |
dc.contributor.author | Serna, Marina | |
dc.contributor.author | Llorca Blanco, Oscar Antonio | |
dc.date.accessioned | 2022-03-03T11:08:47Z | |
dc.date.available | 2022-03-03T11:08:47Z | |
dc.date.issued | 2022-02-02 | |
dc.identifier.citation | Nucleic Acids Res. 2022 Jan 25;50(2):1128-1146. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/13716 | |
dc.description.abstract | Biogenesis of the U5 small nuclear ribonucleoprotein (snRNP) is an essential and highly regulated process. In particular, PRPF8, one of U5 snRNP main components, requires HSP90 working in concert with R2TP, a cochaperone complex containing RUVBL1 and RUVBL2 AAA-ATPases, and additional factors that are still poorly characterized. Here, we use biochemistry, interaction mapping, mass spectrometry and cryoEM to study the role of ZNHIT2 in the regulation of the R2TP chaperone during the biogenesis of PRPF8. ZNHIT2 forms a complex with R2TP which depends exclusively on the direct interaction of ZNHIT2 with the RUVBL1-RUVBL2 ATPases. The cryoEM analysis of this complex reveals that ZNHIT2 alters the conformation and nucleotide state of RUVBL1-RUVBL2, affecting its ATPase activity. We characterized the interactions between R2TP, PRPF8, ZNHIT2, ECD and AAR2 proteins. Interestingly, PRPF8 makes a direct interaction with R2TP and this complex can incorporate ZNHIT2 and other proteins involved in the biogenesis of PRPF8 such as ECD and AAR2. Together, these results show that ZNHIT2 participates in the assembly of the U5 snRNP as part of a network of contacts between assembly factors required for PRPF8 biogenesis and the R2TP-HSP90 chaperone, while concomitantly regulating the structure and nucleotide state of R2TP. | es_ES |
dc.description.sponsorship | Agencia Estatal de Investigación (AEI/10.13039/501100011033), Ministerio de Ciencia e Innovación and co-funded by the European Regional Development Fund (ERDF-UE) [SAF2017-82632-P and PID2020-114429RB-I00 to O.L.]; Autonomous Region of Madrid and co-funded by the European Social Fund and the European Regional Development Fund [Y2018/BIO4747 and P2018/NMT4443 to O.L., and which support the contracts of S.C. and A.G-C.]; Funding for open access charge: Agencia Estatal de Investigación (AEI/10.13039/501100011033), Ministerio de Ciencia e Innovación, co-funded by the European Regional Development Fund (ERDF-UE) [SAF2017-82632-P to O.L.]; S.C. contract is funded by the CNIO Friends Program philanthropic initiative since June 2021. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | ATPases Associated with Diverse Cellular Activities | es_ES |
dc.subject.mesh | Carrier Proteins | es_ES |
dc.subject.mesh | DNA Helicases | es_ES |
dc.subject.mesh | HEK293 Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Phosphoproteins | es_ES |
dc.subject.mesh | Protein Binding | es_ES |
dc.subject.mesh | RNA Precursors | es_ES |
dc.subject.mesh | RNA Splicing | es_ES |
dc.subject.mesh | RNA, Messenger | es_ES |
dc.subject.mesh | RNA-Binding Proteins | es_ES |
dc.title | CryoEM of RUVBL1-RUVBL2-ZNHIT2, a complex that interacts with pre-mRNA-processing-splicing factor 8. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 34951455 | es_ES |
dc.format.volume | 50 | es_ES |
dc.format.number | 2 | es_ES |
dc.format.page | 1128-1146 | es_ES |
dc.identifier.doi | 10.1093/nar/gkab1267 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación | es_ES |
dc.contributor.funder | Comunidad de Madrid | es_ES |
dc.contributor.funder | European Regional Development Fund | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1362-4962 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1093/nar/gkab1267. | es_ES |
dc.identifier.journal | Nucleic acids research | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Complejos Macromoleculares en la Respuesta a Daños en el DNA | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/PID2020-114429RB-I00 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/P2018/NMT4443 t | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/SAF2017-82632-P | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/PID2020-114429RB-I00 | es_ES |